Poststroke seizures and epilepsy have been described in numerous clinical and population studies. In contrast, the pathophysiological events of injured brain that establish poststroke epileptogenesis are not well understood because animal modelinq has had limited development (Kelly, 2002). In the elderly, stroke is the dominant cause of epilepsy yet the modeling of poststroke epilepsy in aged animals has had only preliminary study (Kelly et al., 2001a). Recent studies in our laboratory have indicated that the technique of cortical photothrombosis and brain infarction can result in poststroke epilepsy in young adult rats characterized electrically by seizures originating in the peri-infarct area and behaviorally by motor arrest of the animal (Kelly et al., 2001a, Kharlamov et al., submitted). In contrast, mid-aged and aged animals demonstrated behavioral seizures characterized by brief but relatively intense rhythmic body jerking associated with focal features (Kelly et al., 2001a). We hypothesize that poststroke epileptogenesis is expressed differentially in an aging-related manner and propose to more appropriately model poststroke epilepsy in the elderly by using photothrombosis and an aging paradigm. Specific Aim #1 will characterize, compare, and contrast the electroencephalographic, behavioral, and neuroanatomical properties of 4 and 20 mo old F344 rats during epileptogenesis and the epileptic state. During photothrombosis, NMDA receptor-mediated events have been implicated in establishing subsequent cortical hyperexcitability, which could lead to the development of epileptic seizures. We hypothesize that neuroprotection limiting glutamate-mediated excitotoxicity associated with photothrombosis will prevent poststroke epileptogenesis. Specific Aim #2 will determine whether MK-801, a non-competitive NMDA receptor antagonist, is capable of preventing poststroke epileptogenesis and whether animal age is a critical variable. The short-term goals of these studies are to establish a reliable animal model of poststroke epilepsy in the elderly and to begin neuroprotection studies designed to prevent or limit poststroke epileptogenesis. The long-term goal of these studies is to advance understanding of the progressive anatomic and physiologic changes of aged brain during poststroke epileptogenesis so that the focus of therapeutic strategies can shift from control of symptoms (seizures) to prevention and cure.